Dual arterial cannulation for aortic surgical procedures in adult sheep.

BACKGROUND/AIMS: Preclinical site-specific placement of valvular prostheses is highly recommended to fully appreciate hemodynamics. An ovine model is commonly used for preclinical prosthetic mitral valve evaluation; however, the ideal animal model for prosthetic aortic valve evaluation has yet to be determined. Past studies have utilized adult sheep for prosthetic aortic valve replacement; however, an anatomically short length of the ascending aorta can present a surgical challenge during implantation. Due to this anatomically short length of the ascending aorta, we designed an arterial cannulation technique for cardiopulmonary bypass (CPB) to provide a more ideal operative setting. METHODS: Dual arterial cannulation for CPB was used in adult Polypay sheep (n = 15) subjected to an aortic root/valve surgical procedure. RESULTS: The arterial cannulation technique described in this paper was successful in performing aortic root/valve surgical procedures in adult sheep. All animals survived the operative procedure without complications. Postoperatively, all animals were alert, neurologically intact and assumed normal daily functions following extubation, which continued throughout their survival. CONCLUSIONS: The use of this arterial cannulation technique was safe, provided better visualization of the aortic root/valve area, less difficulty in performing the aortic root/valve surgical procedure, and less observed tissue tension while closing the aortotomy.

D-ribose--an additive with caffeine.

Caffeine acts as a stimulant, in which approximately 90% of people in the United States consume daily. Besides its beneficial effects, many individuals have experienced unpleasant reactions following the consumption of caffeine: such as insomnia, an increase in heart rate, feelings of nervousness, headaches, occasional lightheadedness, a state of "jitters," and a potential "crash" state following its metabolism. Researchers have proposed mechanisms responsible for caffeine's interactions, which include its blocking capacity of adenosine receptors, its role with the pituitary gland, increasing levels of dopamine, and its role with the intracellular release of calcium from the sarcoplasmic reticulum, which is dependent on intracellular adenosine triphosphate levels. Specific substrates have been investigated to lessen the undesirable effects of caffeine and still preserve its stimulatory benefits. The results of these investigations have produced no positive consensus. However, D-ribose, an important pentose carbohydrate in the energy molecule of adenosine triphosphate, as well as our genetic code and other cellular processes, could offer such a solution to this problem. D-ribose could potentially aid in maintaining or potentially lowering extra-cellular adenosine concentrations, aid in the flux of intracellular calcium, aid in intracellular energy production, and potentially lessen the perceived "crash" state felt by many. Every cell requires adequate levels of energy to maintain its integrity and function. Caffeine has the potential to task this energy equilibrium. D-ribose with caffeine may be the substrate to aid in the potential intracellular energy demand, aid in lessening the perceived unpleasant side effects of caffeine, and still preserving the desired benefits of this stimulant consumed by all of us daily.

Effects on C3 and CH50 levels during and following extracorporeal whole body hyperthermia.

Cardiopulmonary bypass can affect inflammatory reactions and evoke the "postperfusion syndrome," manifested as multiple organ dysfunction in the recovery period. This syndrome is generated by the activation of complement, macrophages, neutrophils, and inflammatory cytokines. Following the use of hypothermia during cardiac procedures, active hyperthermic rewarming is used to reestablish body temperature. Complement levels and their interactions have been investigated during and following hypothermia. Hyperthermia is being used clinically; however, the effect of markedly elevated temperatures on complement is unknown and, therefore, needs to be investigated. A pilot canine study was designed to begin to explore what role hyperthermia may play on complement levels during and following extracorporeal whole body hyperthermia. Five dogs were heated to a core temperature of approximately 42 degrees C, held at this elevated temperature for 90 minutes, then cooled to normothermia. A decline in C3 levels at the end of warming with further declines through day 4 post treatment was observed. CH50 levels mimicked the C3 level decline; however, there was a trend for rebounding by day 4. The findings involving complement factors following hyperthermia signify that this increase in temperature causes a decrease in both C3 and CH50 levels.

Extracorporeal whole body hyperthermia treatment of HIV patients, a feasibility study.

The literature supports that the retrovirus, Human Immunodeficiency Virus (HIV), which is thought to cause Acquired Immunodeficiency Syndrome (AIDS), is heat sensitive at temperatures which can be achieved in man. Invasive or non-invasive induction of whole body hyperthermia (WBH) has been used to treat an array of illnesses, primarily in the field of oncology, until recently. Non-invasive methods have proven to be less toxic than invasive means. However, new technology and refined patient management have shown a dramatic decrease in the side effects with extracorporeal whole body hyperthermia (EWBH). The Food and Drug Administration granted a prospective trial for six HIV positive/AIDS patients to undergo a single treatment of EWBH, with patients randomized to a core temperature of either 41 or 42 degrees C. All patients had failed antiretrovirals and experienced at least one episode of an opportunistic infection. Organetics, Ltd., PS-1 extracorporeal, centrifugal pump device was used to induce EWBH. Results of this feasibility study demonstrated the ability of this equipment and technique to induce EWBH with acceptable toxicity. It was not possible to assess efficacy in this small study.

Effects of Hypoxia on the Pulmonary Microvascular Permeability in Adult Rabbit Lung.

Within the last 30 years, researchers have explored what role hypoxia might play in causing permeability changes in the pulmonary microvasculature. Since the data accumulated thus far are unclear, the effects of hypoxia on microvascular transport in the isolated, Ringer's perfused adult rabbit lung was observed and the following parameters were measured or computed for both oxygenated and hypoxic perfusates: pulmonary arterial (r(a)) and pulmonary venous (r(v)) resistances, pulmonary capillary filtration coefficients (K(f)), and pulmonary capillary endothelial reflection coefficients (sigma) for NaCl and inulin. Separate reservoir bottles were used to create the desired oxygenated (aeration of solution with 95% O(2)-5% CO(2)) gas mixture or hypoxic (aeration of solution with 95% N(2)-5% CO(2)) gas mixture. A higher, but not significant, resistance value was found during the oxygenated state. A significant increase in the pulmonary capillary filtration coefficient during hypoxia (10.72 x 10(-4) +/- 0.446 x 10(-4) cm(3)/s cm H(2)O for the hypoxic perfusate and 8.80 x 10(-4) +/- 0.384 x 10(-4) cm(3)/s cm H(2)O for the oxygenated perfusate) was found and a significant difference between oxygenated and hypoxic pulmonary capillary reflection coefficients for inulin was computed (oxygenated solution revealed a finding of 0.120 +/- 0.003 and the hypoxic solution revealed 0.105 +/- 0.002). These findings imply a change in the microvascular permeability during hypoxia. According to the pore theory, a change in pore number, pore size, or both could have occurred. However, from the reflection coefficient data, a change in pore radius seems most likely. Copyright 1995 S. Karger AG, Basel

Rise in plasma beta-endorphin, ACTH, and cortisol in cancer patients undergoing whole body hyperthermia.

It has been previously reported that sauna-induced fevers (approximately 39 degrees C) result in rises of beta-endorphins in normal volunteers. This report describes changes in plasma beta-endorphins in cancer patients undergoing whole body hyperthermia (40.5 degrees C to 41.8 degrees C). Results presented show that there is a linear relationship between thermal stress, defined in terms of core temperature and/or duration of hyperthermia, and the quantitative rise in plasma beta-endorphin levels. Data relating to changes in ACTH and cortisol levels are in a single temperature range (41.5 degrees C--41.8 degrees C) are also reported.

Neuroendocrine changes in patients undergoing whole body hyperthermia.

A phase I study of whole body hyperthermia (WBH) (52 treatments/12 patients) utilizing a radiant heat device has been completed. This study incorporated a temperature escalation scheme from 39.5 to 41.8 degrees C for up to 150 min. Pain relief or a sense of well being was observed post-WBH in the first three patients entered in this study. We postulated that WBH might result in increases in the opiate peptide beta-endorphin. Therefore we elected to study prospectively the next six patients entered in this study to test the hypothesis that WBH stimulates the neuroendocrine axis. Results are reported which show thermal-induced increases in plasma levels of beta-endorphin as well as prolactin, ACTH and cortisol.

A nontoxic system for 41.8 degrees C whole-body hyperthermia: results of a Phase I study using a radiant heat device.

A Phase I study of whole-body hyperthermia (WBH) (52 treatments/12 patients) was completed with no significant clinical toxicity. The study incorporated a thermal dose escalation scheme from 39.5 degrees-41.8 degrees C for up to 151 min. A radiant-heat device was utilized for producing WBH. During WBH, patients were sedated; endotracheal intubation was not required. No changes in cardiovascular, respiratory, hematological, or biochemical indices requiring clinical intervention occurred during the study. We conclude the radiant-heat device coupled with a defined pharmacological approach to WBH with appropriate patient screening yields a system for 41.8 degrees C WBH which is safe and efficient, is not labor intensive, and does not require general anesthesia and endotracheal intubation. This system is appropriate for a multimodality approach to various systemic cancers.

Whole body hyperthermia (41-42 degrees C): a simple technique for unanesthetized mice.

A technique for accomplishing 41-42 degrees C whole body hyperthermia (WBH) in unrestrained, unanesthetized mice using a simple apparatus is reported. This method combines a radiant heat technology with monitoring of individual rectal temperatures at 10-min intervals. In 66 heating sessions, involving 116 AKR mice and a total of 619 WBH treatments, the mortality rate was less than 1%. Treatment at 41-42 degrees C for periods of up to 120 min were accomplished. Relationships of several variables of mouse temperature-time profiles were studied including (1) initial core temperature, (2) rate of heating, (3) whole body irradiation, and (4) the presence of tumor (transplanted AKR leukemia). Sham treatments produce a consistent temperature-time profile showing about a 1 degree C rise. Between-mouse variability, as well as between-treatment variability in individual animals was estimated. Thermal mapping of the device demonstrates a range from 32-38 degrees C of the air temperature in the zone with the mice to a high of 47 degrees C near to the radiant heating surface at the top of the apparatus.

Whole body hyperthermia with a microwave regional boost: unexpected toxicity in the pig.

An animal model was used to investigate the potential for delivering a regional temperature boost using microwave energy after whole body hyperthermia had been induced in a pig using low density, radiant heat. Thermal profiles and an unexpected toxicity in the region of the microwave energy deposition, which included the heart and liver, are reported.